A method for treating, decreasing the severity and/or progression of, or preventing fibrosis and/or related diseases, or treating, decreasing the severity and/or progression of, and/or preventing autophagy and/or related diseases, or for inhibiting autophagy flux, or inhibiting cathepsins B (CTSB), L (CTSL) and/or D (CTSD) and/or related diseases, comprising administering an effective amount of a compound of Formula (I)
- wherein
- L1 is selected from the group consisting of a single bond;
- optionally substituted alkyl, said optionally substituted alkyl being or not further substituted by at least one R6;
- optionally substituted cycloalkyl;
- optionally substituted alkenyl;
- optionally substituted cycloalkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkynyl;
- —C═O;
- —SO;
- —SO2;
- —(C═O)—NR8;
- —(C═O)—O;
- —(C═O)—O-alkyl;
- —SO2—NR8;
- and —NR8,
- R1 is an optionally substituted aryl, said optionally substituted aryl being or not further substituted by at least one R9;
- or an optionally substituted heteroaryl, said optionally substituted heteroaryl being or not further substituted by at least one R9,
- R2 and R3 are independently selected from the group consisting of hydrogen;
- —(CO)—R7;
- —(CO)—O—R7;
- —(CO)—NR8OH;
- —(CO)—NR12OH;
- —(CO)—NR8R8′;
- —(CO)—NR12R13;
- —SO2—R7;
- —SO2—NR8R8′;
- —SO2—NR12R13;
- optionally substituted alkyl;
- optionally substituted cycloalkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkenyl;
- optionally substituted cycloalkynyl;
- optionally substituted aryl;
- optionally substituted benzyl;
- optionally substituted heteroaryl;
- optionally substituted heterocyclyl;
- or R2 and R3 can be linked together with nitrogen to which they are covalently linked to form an optionally substituted heterocyclyl,
- R2′ is selected from the group consisting of hydrogen;
- optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkyl;
- optionally substituted cycloalkenyl;
- and optionally substituted cycloalkynyl;
- optionally substituted heterocyclyl,
- R4 is, alone or simultaneously or independently when n>1, selected from the group consisting of hydrogen;
- halogen;
- optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkyl;
- optionally substituted cycloalkenyl;
- optionally substituted cycloalkynyl;
- optionally substituted alkoxy;
- hydroxyl;
- nitro;
- azido;
- cyano;
- NR12R13;
- NR8R8′;
- —O—(R7);
- —(CO)—R7;
- —(CO)—O—R7;
- —(CO)—NR12OH;
- —(CO)—NR8OH;
- —(CO)—NR12R13;
- —(CO)—NR8R8′;
- —O—(CO)—R7;
- —O—(CO)—NR12R13;
- —O—(CO)—NR8R8′;
- —NR12—(CO)—R7;
- NR8—(CO)—R7;
- —NR12—(CO)—OR7;
- NR8—(CO)—OR7;
- —O—(CO)—OR7;
- —NR12—(CO)—NR12R13;
- —NR8—(CO)—NR8R8′;
- —(O—CH2CH2)p—OR22;
- —(O—CH2CH2)p—OR7;
- —(O—CH2CH2)p—NR12R13;
- —(O—CH2CH2)p—NR8R8′;
- NR12—(CH2CH2—O)p—R13;
- —NR8—(CH2CH2—O)p—R7;
- —SO2—R7;
- —NR12—SO2—R7;
- —NR8—SO2—R7;
- —SO2—NR12R13;
- —SO2—NR8R8′;
- —NR12—SO2—NR12R13;
- NR8—SO2—NR8R8′;
- —NR12—(C2-C8)-alkyl-NR12R13;
- NR8—(C2-C8)-alkyl-NR8R8′;
- —NR12—(C2-C8)-alkyl-OR13;
- NR8—(C2-C8)-alkyl-OR7, optionally substituted aryl;
- optionally substituted heteroaryl;
- and optionally substituted heterocyclyl,
- R5 is selected from the group consisting of hydrogen;
- halogen;
- hydroxyl;
- optionally substituted alkoxy;
- NR2′R10;
- —O—R10;
- nitro;
- azido;
- cyano;
- NR12R13;
- —NR8R8′;
- —(CO)—R7;
- —(CO)—O—R7;
- —(CO)—NR12OH;
- —(CO)—NR8OH;
- —(CO)—NR12R13;
- —(CO)—NR8R8′;
- —O—(CO)—R7;
- —O—(CO)—NR12R13;
- —O—(CO)—NR8R8′;
- NR12—(CO)—R7;
- NR8—(CO)—R7;
- NR12—(CO)—OR7;
- NR8—(CO)—OR7;
- —O—(CO)—OR7;
- NR12—(CO)—NR12R13;
- —NR8—(CO)—NR8R8′;
- —SO2—R7;
- —NR12—SO2—R7;
- NR8—SO2—R7;
- —SO2—NR12R13;
- —SO2—NR8R8′;
- NR12—SO2—NR12R13;
- NR8—SO2—NR8R8′;
- NR12—(C2-C10)-alkyl-NR12R13;
- NR8—(C2-C10)-alkyl-NR8R8′;
- NR12—(C2-C10)-alkyl-OR13;
- NR8—(C2-C10)-alkyl-OR7;
- —O(R7);
- —(O—CH2CH2)p—OR12;
- —(O—CH2CH2)p—OR7;
- —(O—CH2CH2)p—NR12R13;
- —(O—CH2CH2)p—NR8R8′;
- —NR12—(CH2CH2—O)p—R13;
- —NR8—(CH2CH2—O)p—R7;
- optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkyl;
- optionally substituted cycloalkenyl;
- optionally substituted cycloalkynyl;
- optionally substituted alkoxy;
- optionally substituted aryl;
- optionally substituted heteroaryl;
- and optionally substituted heterocyclyl,
- R6 is simultaneously or independently selected from the group consisting of hydrogen atom;
- optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkyl;
- optionally substituted cycloalkenyl;
- optionally substituted cycloalkynyl;
- optionally substituted aryl;
- optionally substituted heteroaryl;
- optionally substituted heterocyclyl;
- and optionally substituted alkoxy,
- R7 is selected from the group consisting of hydrogen;
- optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkyl;
- optionally substituted cycloalkenyl;
- optionally substituted cycloalkynyl;
- optionally substituted aryl;
- optionally substituted heteroaryl;
- and optionally substituted heterocyclyl,
- R8 and R8′ are simultaneously or independently selected from the group consisting of hydrogen;
- optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkyl;
- optionally substituted cycloalkenyl;
- optionally substituted cycloalkynyl;
- optionally substituted heterocyclyl;
- optionally substituted aryl;
- and optionally substituted heteroaryl;
- or R8 and R8′ are linked together with nitrogen to which they are covalently linked to form an optionally substituted heterocyclyl group,
- R9 is simultaneously or independently selected from the group consisting of hydrogen;
- halogen;
- hydroxyl;
- NR2′R10;
- —O—R10;
- nitro;
- azido;
- cyano;
- —NR12R13;
- —NR8R8′;
- —(CO)—R7;
- —(CO)—O—R7;
- —(CO)—NR12OH;
- —(CO)—NR8OH;
- —(CO)—NR12R13;
- —(CO)—NR8R8′;
- —O—(CO)—R7;
- —O—(CO)—NR12R13;
- —O—(CO)—NR8R8′;
- NR12—(CO)—R7;
- NR8—(CO)—R7;
- NR12—(CO)—OR7;
- NR8—(CO)—OR7;
- —O—(CO)—OR7;
- —NR12—(CO)—NR12R13;
- NR8—(CO)—NR8R8′;
- —SO2—R7;
- NR12—SO2—R7;
- NR8—SO2—R7;
- —SO2—NR12R13;
- —SO2—NR8R8′;
- NR12—SO2—NR12R13;
- NR8—SO2—NR8R8′;
- NR12—(C2-C10)-alkyl-NR12R13;
- NR8—(C2-C10)-alkyl-NR8R8′;
- NR12—(C2-C10)-alkyl-OR13;
- NR8—(C2-C10)-alkyl-OR7;
- —O(R7);
- —(O—CH2CH2)p—OR12;
- —(O—CH2CH2)p—OR7;
- —(O—CH2CH2)p—NR12R13;
- —(O—CH2CH2)p—NR8R8′;
- —NR12—(CH2CH2—O)p—R13;
- —NR8—(CH2CH2—O)p—R7;
- optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkyl;
- optionally substituted cycloalkenyl;
- optionally substituted cycloalkynyl;
- optionally substituted alkoxy;
- optionally substituted aryl;
- optionally substituted heteroaryl;
- and optionally substituted heterocyclyl,
- R10 is selected from the group consisting of hydrogen;
- optionally substituted aryl said optionally substituted aryl being or not further substituted by one or more R11;
- optionally substituted heteroaryl said optionally substituted heteroaryl being or not further substituted by one or more R11;
- optionally substituted heterocyclyl, said optionally substituted heterocyclyl group being or not further substituted by one or more R11,
- R11 is simultaneously or independently selected from the group consisting of hydrogen;
- halogen;
- optionally substituted alkoxy;
- hydroxyl;
- nitro;
- cyano;
- azido;
- —NR12R13;
- —NR8R8′;
- —O—(R8);
- —(CO)—R8;
- —(CO)—O—R8;
- —(CO)—NR12OH;
- —(CO)—NR8OH;
- —(CO)—NR12R13;
- —(CO)—NR8R8′;
- —O—(CO)—R8;
- —O—(CO)—NR12R13;
- —O—(CO)—NR8R8′;
- —NR12—(CO)—R8;
- —NR8—(CO)—R8′;
- —NR12—(CO)—OR8;
- —NR8—(CO)—OR8′;
- —O—(CO)—OR8;
- —NR12—(CO)—NR12R13;
- —NR8—(CO)—NR8R8′;
- —(O—CH2CH2)p—OR12;
- —(O—CH2CH2)p—OR8;
- —(O—CH2CH2)p—NR12R13;
- —(O—CH2CH2)p—NR8R8′;
- —NR12(—CH2CH2—O)p—R13;
- —NR8(—CH2CH2—O)p—R8′;
- —SO2—R8;
- —NR12—SO2—R8;
- —NR8—SO2—R8′;
- —SO2—NR12R13;
- —SO2—NR8R8′;
- —NR12—SO2—NR12R13;
- —NR8—SO2—NR8R8′;
- —NR12—(C2-C5)-alkyl-NR12R13;
- —NR8—(C2-C8)-alkyl-NR8R8′;
- —NR12—(C2-C8)-alkyl-OR13;
- —NR8—(C2-C8)-alkyl-OR8′;
- optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkyl;
- optionally substituted cycloalkenyl;
- optionally substituted cycloalkynyl;
- optionally substituted aryl;
- optionally substituted heteroaryl;
- and optionally substituted heterocyclyl,
- R12 and R13 are simultaneously or independently selected from the group consisting of hydrogen;
- —(CO)—R7;
- —(CO)—O—R7;
- —(CO)—NR8OH;
- —(CO)—NR8R8′;
- —SO2—R7;
- —SO2—NR8R8′;
- optionally substituted alkyl;
- optionally substituted alkenyl;
- optionally substituted alkynyl;
- optionally substituted cycloalkenyl;
- optionally substituted cycloalkynyl;
- optionally substituted aryl;
- optionally substituted heteroaryl;
- and optionally substituted heterocyclyl;
- or R12 and R13 are linked together with the nitrogen atom to which they are covalently linked to form an optionally substituted heterocyclyl,
- n is 0, 1, 2, 3 or 4,
- m is 1, 2 or 3,
- p is 1, 2, 3, 4 or 5,
- and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, polymorphs, tautomers, isotopic variants, isomers, stereoisomers or mixtures of stereoisomers thereof, to a patient in need of treatment thereof.